Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC
GLOBETECH MEDIA

Novel Drug Blocks Activity of Toxic Alzheimer's Disease Peptides

By BiotechDaily International staff writers
Posted on 19 Dec 2013
Image: Micrograph of an adult Caenorhabditis elegans (Photo courtesy of Wikimedia Commons).
Image: Micrograph of an adult Caenorhabditis elegans (Photo courtesy of Wikimedia Commons).
Drug developers have identified a compound that in a worm model blocks the action of the type of toxic peptide plaques that characterize human neurodegenerative diseases such as Alzheimer's and Huntington's.

Aging manipulation is an emerging strategy aimed to postpone the manifestation of late-onset neurodegenerative disorders such as Alzheimer's (AD) and Huntington's diseases (HD) and to slow their progression once emerged. Investigators at the Hebrew University of Jerusalem (Israel) and their colleagues at the biopharmaceutical start-up company TyrNovo (Herzliya, Israel) had shown previously that reducing the activity of the insulin/IGF signaling cascade (IIS), a prominent aging-regulating pathway, protected nematode worms (Caenorhabditis elegans) from the toxicity of various aggregative proteins, including the AD-associated peptide, A-beta and the HD-linked peptide, polyQ40.

In the current study the investigators worked with an AD model based on a variant of C. elegans that expresses the highly aggregative, human AD-associated peptide, A-beta-42, in their body wall muscles. The expression of A-beta in these animals leads to a progressive paralysis within the worm population. The investigators treated the A-beta-42 worms with TyrNovo's novel compound NT219. NT219 possesses a unique mechanism, which leads to the elimination of IRS 1/2 and the long-term blockage of all signals they transmit.

Results published in the November 22, 2013, online edition of the journal Aging Cell revealed that NT219 mediated a long-lasting, highly efficient inhibition of the IIS signaling cascade by a dual mechanism. It reduced the autophosphorylation of the IGF1 receptor and directed the insulin receptor substrates 1 and 2 (IRS 1/2) for degradation. NT219 treatment promoted stress resistance and protected nematodes from the toxicity of AD- and HD-associated peptides without affecting the lifespan of the organism.

"The findings of the study reinforces the claim that blocking the signaling pathway of insulin and the growth hormone IGF1, a pathway known to be a central controller of the aging process in worms and mammals, can potentially be used as a treatment for degenerative brain diseases," said senior author Dr. Ehud Cohen, professor of biochemistry and molecular biology at the Hebrew University of Jerusalem. "The new findings are the first evidence that a pharmacological substance can effectively protect against toxicity of proteins associated with neurodegenerative diseases, through selective inhibition of the aging process."

The investigators have filed a patent application based on this study that includes the rights for use of NT219 as a therapeutic agent.

Related Links:

Hebrew University of Jerusalem



Channels

Genomics/Proteomics

view channel
Image: The osteochondroretricular stem cell is a newly identified type of bone stem cell that appears to be vital to skeletal development and may provide the basis for novel treatments for osteoarthritis, osteoporosis, and bone fractures. In this illustration of the head of a femur, osteochondroretricular stem cells are visualized in red (Photo courtesy of Dr. Timothy Wang, Columbia University).

Gremlin 1 Expression Distinguishes Stem Cells Able to Regenerate Bones and Cartilage in Adult Mice

A newly identified type of stem cell in the bone marrow of adult mice was found to be capable of regenerating both bone and cartilage. Investigators at Columbia University (New York, NY, USA) reported... Read more

Biochemistry

view channel

Blocking Enzyme Switch Turns Off Tumor Growth in T-Cell Acute Lymphoblastic Leukemia

Researchers recently reported that blocking the action of an enzyme “switch” needed to activate tumor growth is emerging as a practical strategy for treating T-cell acute lymphoblastic leukemia. An estimated 25% of the 500 US adolescents and young adults diagnosed yearly with this aggressive disease fail to respond to... Read more

Therapeutics

view channel
Image: Cancer cells infected with tumor-targeted oncolytic virus (red). Green indicates alpha-tubulin, a cell skeleton protein. Blue is DNA in the cancer cell nuclei (Photo courtesy of Dr. Rathi Gangeswaran, Bart’s Cancer Institute).

Innovative “Viro-Immunotherapy” Designed to Kill Breast Cancer Cells

A leading scientist has devised a new treatment that employs viruses to kill breast cancer cells. The research could lead to a promising “viro-immunotherapy” for patients with triple-negative breast cancer,... Read more

Lab Technologies

view channel
Image: MIT researchers have designed a microfluidic device that allows them to precisely trap pairs of cells (one red, one green) and observe how they interact over time (Photo courtesy of Burak Dura, MIT).

New Device Designed to See Communication between Immune Cells

The immune system is a complicated network of many different cells working together to defend against invaders. Effectively combating an infection depends on the interactions between these cells.... Read more

Business

view channel

Program Designed to Provide High-Performance Computing Cluster Systems for Bioinformatics Research

Dedicated Computing (Waukesha, WI, USA), a global technology company, reported that it will be participating in the Intel Cluster Ready program to deliver integrated high-performance computing cluster solutions to the life sciences market. Powered by Intel Xeon processors, Dedicated Computing is providing a range of... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.